Pharmacogenomic application of the haptoglobin genotype in the treatment of HDL dysfunction

Pharmacogenomic application of the haptoglobin genotype in the treatment of HDL dysfunction
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结合珠蛋白基因型在治疗 HDL 功能障碍中的药物基因组学应用

DOI:
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发表时间:
2009
影响因子:
1.9
通讯作者:
A. Levy
A. Levy
中科院分区:
医学4区
文献类型:
--
作者:
Avery Schwartz;S. Blum;R. Asleh;M. Pollak;Shiri Kalet;A. Levy

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一个新兴的研究范式表明,在糖尿病(DM)的设置中,高密度脂蛋白(HDL)的质量或功能可能是心血管疾病风险的决定因素。已经提出由氧化修饰引起的HDL蛋白质和脂质组分的特定结构修饰介导HDL丧失促进胆固醇流出(反向胆固醇转运)的能力,用作抗氧化剂和抗炎剂。因此,抑制HDL氧化修饰有望改善其功能并提供心脏保护。然而,抗氧化剂策略,以减少糖尿病动脉粥样硬化心血管事件已经失败。有人提出,这一失败可能是由于患者选择的性质不充分。高剂量抗氧化剂治疗可能仅对氧化修饰HDL的一部分DM个体有益。我们将回顾结合珠蛋白(Hp)识别这些个体的证据,这些个体可以成功地用维生素E治疗。这些数据表明,利用Hp基因型的药物基因组学方法可能有助于识别从抗氧化治疗中获益的个体。
An emerging paradigm of research has suggested that in the setting of diabetes mellitus (DM) the quality or function of high-density lipoprotein (HDL) may be a determinant of cardiovascular disease risk. Specific structural modifications of HDL protein and lipid components, resulting from oxidative modification, have been proposed to mediate HDL’s loss of the ability to promote cholesterol efflux (reverse cholesterol transport), serve as an antioxidant and anti-inflammatory agent. Therefore, inhibiting HDL oxidative modification would be expected to improve its function and provide cardioprotection. Nevertheless, antioxidant strategies to reduce cardiovascular events from atherosclerosis in DM have failed. It has been proposed that this failure may have been due to the inadequate nature of patient selection. High dose antioxidant therapy may only provide benefit to a subset of DM individuals with oxidatively modified HDL. We will review evidence that haptoglobin (Hp) identifies such individuals who can be successfully treated with vitamin E. These data will suggest that a pharmacogenomic approach utilizing the Hp genotype may be useful in identifying individuals who will benefit from antioxidant therapy.
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